Exploring the safety of propylene glycol based on the NTP-CERHR Monograph on reproductive and developmental effects
Propylene glycol (PG) is a small, colorless, odorless compound that quietly performs essential functions in thousands of consumer products.
PG keeps our toothpaste moist, helps medications remain stable, and is found in many lotions and creams.
PG allows paints to flow smoothly and is used in antifreeze formulations as a safer alternative to ethylene glycol.
Given its widespread presence in items we use daily, an important question emerges: how safe is this invisible ingredient, particularly for the most vulnerable among us—pregnant women and developing children? 2
Propylene glycol (1,2-propanediol) is a hydroxy-substituted hydrocarbon with alcohol groups on adjacent carbon atoms 3 .
The liver enzyme alcohol dehydrogenase (ADH) breaks down PG into lactate and pyruvate 1 .
FDA has granted PG "Generally Recognized As Safe" (GRAS) status for use in foods 1 .
When propylene glycol enters the human body, primarily through ingestion, it undergoes a sophisticated metabolic process. The rate at which our bodies can process propylene glycol varies significantly by age—a critical factor that regulatory agencies must consider when setting safety guidelines.
Adult livers efficiently metabolize PG through the ADH pathway.
Neonatal livers possess significantly less capacity, making infants potentially more vulnerable 1 .
Recent research shows that alcohol dehydrogenase enzyme becomes saturated at certain PG concentration levels 1 .
While cell cultures and computer simulations provide valuable preliminary data, only whole living systems can reveal how a substance affects complex processes like embryonic development, organ formation, and multi-generational reproductive health 3 .
Scientists use controlled laboratory experiments with animals to answer fundamental questions about chemical safety.
For ethical reasons, we cannot conduct these invasive, highly controlled studies in humans.
Carefully designed and humanely conducted animal research remains essential for safety assessment 3 .
When Metabolism Falters
A 2024 study demonstrated that the alcohol dehydrogenase enzyme responsible for breaking down PG becomes saturated at certain concentration levels 1 .
To thoroughly assess propylene glycol's potential effects, the NTP-CERHR expert panel examined data from multiple well-designed animal studies following a "continuous breeding protocol" in mice 3 .
| Aspect | Details |
|---|---|
| Species | Mice |
| Administration | Drinking water |
| Dose Concentrations | 0% to 30% (w/w) PG in feed |
| Exposure Duration | Continuous across generations |
| Parameters Measured | Mating success, litter size, offspring viability |
The results of these comprehensive reproductive studies proved remarkably consistent—and surprisingly reassuring. Even at the highest doses tested, researchers observed no adverse effects on fertility in either male or female mice 3 .
| Species | Highest Dose Tested | Developmental Effects | Maternal Toxicity |
|---|---|---|---|
| Mice | 10,400 mg/kg/day | None observed | None at lower doses |
| Rats | 1,600 mg/kg/day | None observed | None observed |
| Hamsters | 1,550 mg/kg/day | None observed | None observed |
| Rabbits | 1,230 mg/kg/day | None observed | None observed |
Mice exposed to doses up to 10,100 mg/kg body weight per day showed no impairment in their ability to produce healthy offspring across multiple generations 3 .
| Material/Method | Function in Research | Significance |
|---|---|---|
| Good Laboratory Practice (GLP) | Quality system for research design, conduct, and reporting | Ensures data reliability and regulatory acceptance |
| Animal Models | Stand-ins for human biological responses | Allow controlled studies not possible in humans |
| Human Liver Cytosol | In vitro system for metabolism studies | Reveals species differences in PG processing |
| Gas Chromatography-Mass Spectrometry | Analytical technique for detecting PG and metabolites | Provides precise measurement of biological levels |
| Alcohol Dehydrogenase Enzymes | Key metabolic enzymes for PG breakdown | Helps understand saturation points and species differences |
The comprehensive scientific evaluation of propylene glycol reveals a reassuring safety profile, particularly regarding reproductive and developmental effects.
The National Toxicology Program's expert panel concluded that there is "negligible concern for adverse developmental and reproductive effects in humans at current, proposed, or estimated exposure levels" 2 4 .
This conclusion doesn't mean that propylene glycol is completely free of all potential effects—at extremely high doses, particularly in medically vulnerable populations like premature infants, concerns about accumulation remain valid.
Physiologically based pharmacokinetic modeling continues to refine our understanding of PG behavior in different populations 1 .
Extensive research supports the safety of propylene glycol for reproductive and developmental health at typical exposure levels.